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Preadmission bisphosphonate use improves survival in critically ill
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Critically ill patients who were prescribed bisphosphonates up to 5 years before ICU admission had better survival rates than those who had not used the medications, according to recent study findings published in The Journal of Clinical Endocrinology & Metabolism.
“Bisphosphonates are the mainstay for prevention and/or treatment of osteoporosis,” the researchers wrote. “In addition to fracture reduction, studies have suggested bisphosphonates prolong survival, which cannot be attributed solely to fracture reduction.”
Paul Lee, MBBS, FRACP, PhD, of the department of endocrinology at the Garvan Institute of Medical Research in Sydney, and colleagues evaluated data from 7,830 critically ill patients treated with bisphosphonate therapy before ICU admission at St. Vincent’s Hospital between 2003 and April 2014. Researchers sought to determine the effect of preadmission bisphosphonate therapy on clinical outcome in this population.
Participants with prior bisphosphonate treatment had an in-hospital mortality rate ratio (MRR) of 0.41 (95% CI, 0.24-0.71); this remained significant after adjustment for age, sex, Charlson comorbid disease aggregates, principal diagnosis, admitting unit and ICU admission year (MRR = 0.39; 95% CI, 0.22-0.67). After adding in excluded participants, similar mortality reductions were found for admissions less than 24 hours (MRR = 0.56; 95% CI, 0.4-0.79), all admissions of participants with multiple admissions (MRR = 0.61; 95% CI, 0.41-0.89) and patients with malignancy (MRR = 0.74; 95% CI, 0.48-0.91).
Bisphosphonate use without concurrent vitamin D was linked to improved survival (MRR = 0.32; 95% CI, 0.1-0.97) compared with no use of bisphosphonates or vitamin D. Use of vitamin D alone also improved survival (MRR = 0.49; 95% CI, 0.38-0.62), but it was improved by 22% more when vitamin D was used concurrently with bisphosphonates (MRR = 0.38; 95% CI, 0.2-0.71).
“Preadmission bisphosphonate use was associated with substantially better survival among critically ill patients,” the researchers wrote. “This study suggests bisphosphonate-mediated benefits in critical illness, which may be partly related to modulation of systemic inflammation through antibone resorption. Whether bisphosphonate-associated mortality reduction is a result of its biological actions in bone per se or in other tissues requires investigation in prospective intervention studies.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
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Rifka Schulman, MD, FACE, CNSC
This study outlines a fascinating association between pre-admission use of bisphosphonates and lower in-hospital mortality. As patients with a history of malignancy were excluded, presumably bisphosphonates were prescribed as treatment for osteoporosis within 5 years prior to hospital admission. These results are impressive given that the patients treated with bisphosphonates were older and sicker, but still demonstrated improved mortality outcomes. It has become increasingly recognized that bisphosphonates may have beneficial effects beyond that of bone, possibly relating to anti-inflammatory actions or metabolic effects. The authors of this article describe a possible "bone failure" which may be a component of the multiorgan failure seen in the critically ill patient. Our group presented similar and relevant data at AACE 2015 regarding improved mortality in patients with chronic critical illness following intravenous pamidronate received during hospital admission (publication pending). This article is relevant to every day practice because it gives insight into other possible benefits beyond bone mineral density when deciding about use of bisphosphonates for our patients with osteoporosis.
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